Abstract | BACKGROUND: METHODS: Adult spontaneously hypertensive rats had a 90 minute transient middle cerebral artery occlusion. At the onset of reperfusion they received a single dose of minocycline (3 mg/kg intravenously) or a vehicle. They were studied at multiple time points up to four weeks with magnetic resonance imaging (MRI), immunohistochemistry and biochemistry. RESULTS:
Minocycline significantly reduced the infarct size and prevented tissue loss in the ischemic hemispheres compared to vehicle-treated rats from two to four weeks as measured with MRI. Cerebral blood flow measured with arterial spin labeling (ASL) showed that minocycline improved perfusion. Dynamic contrast-enhanced MRI indicated that minocycline reduced BBB permeability accompanied with higher levels of TJPs measured with Western blot. Increased MMP-2 and -3 were detected at four weeks. Active microglia/macrophage, surrounding and within the peri- infarct areas, expressed YM1, a marker of M2 microglia/macrophage activation, at four weeks. These microglia/macrophage expressed both pro-inflammatory factors tumor necrosis factors-α (TNF-α) and interleukin-1β (IL-1β) and anti-inflammatory factors transforming growth factor-β (TGF-β) and interleukin-10 (IL-10). Treatment with minocycline significantly reduced levels of TNF-α and IL-1β, and increased levels of TGF-β, IL-10 and YM1. CONCLUSIONS: Early minocycline treatment against reperfusion injury significantly promotes neurovascular remodeling during stroke recovery by reducing brain tissue loss, enhancing TJP expression in ischemic brains and facilitating neuroprotective phenotype alternative activation of microglia/macrophages.
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Authors | Yirong Yang, Victor M Salayandia, Jeffrey F Thompson, Lisa Y Yang, Eduardo Y Estrada, Yi Yang |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 12
Pg. 26
(Feb 10 2015)
ISSN: 1742-2094 [Electronic] England |
PMID | 25889169
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- Rec A Recombinases
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
- Minocycline
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Topics |
- Animals
- Blood-Brain Barrier
(drug effects, physiology)
- Cerebrovascular Circulation
(drug effects)
- Cytokines
(metabolism)
- Disease Models, Animal
- Gene Expression Regulation
(drug effects)
- Infarction, Middle Cerebral Artery
(drug therapy, pathology)
- Macrophages
(drug effects)
- Magnetic Resonance Imaging
- Male
- Matrix Metalloproteinase 2
(metabolism)
- Matrix Metalloproteinase 9
(metabolism)
- Microglia
(drug effects)
- Minocycline
(therapeutic use)
- Rats
- Rats, Inbred SHR
- Rec A Recombinases
(metabolism)
- Recovery of Function
(drug effects)
- Reperfusion
- Time Factors
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